FEN1-IN-4 (Compound 2) is a human flap endonuclease-1 (hFEN1) inhibitor.

Physicochemical Properties

Molecular Formula	C12H12N2O3
Molecular Weight	232.2353
Exact Mass	232.084
CAS #	1995893-58-7
PubChem CID	121231495
Appearance	Light yellow to yellow solid powder
LogP	1.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	17
Complexity	354
Defined Atom Stereocenter Count	0
SMILES	O=C1N(C(C2=C([H])C([H])=C([H])C([H])=C2N1C([H])([H])C1([H])C([H])([H])C1([H])[H])=O)O[H]
InChi Key	JAFLWTUYSKADJS-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H12N2O3/c15-11-9-3-1-2-4-10(9)13(7-8-5-6-8)12(16)14(11)17/h1-4,8,17H,5-7H2
Chemical Name	1-(cyclopropylmethyl)-3-hydroxyquinazoline-2,4-dione
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

Because of its role in LP-BER, FEN1 has also emerged as a potential chemosensitizing target because it is essential for repairing methyl mesylate-induced alkylation damage and its knockdown or inhibition increases glutinogenesis. Sensitivity to temozolomide in blastoma and colorectal cancer cell lines[1]. FEN1 inhibition selectively impairs proliferation of colon cancer cells lacking Cdc4 and Mre11a, both of which are frequently mutated in colorectal cancer.

References

[1]. Cellularly Active N-hydroxyurea FEN1 Inhibitors Block Substrate Entry to the Active Site. Nat Chem Biol. 2016 Oct;12(10):815-21.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~538.24 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.3059 mL	21.5295 mL	43.0589 mL
	5 mM	0.8612 mL	4.3059 mL	8.6118 mL
	10 mM	0.4306 mL	2.1529 mL	4.3059 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.